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Article ; Online: Hydroxytyrosol Interference with Inflammaging via Modulation of Inflammation and Autophagy.

Velotti, Francesca / Bernini, Roberta

2023 Volume 15, Issue 7

Abstract: Inflammaging refers to a chronic, systemic, low-grade inflammation, driven by immune (mainly macrophages) and non-immune cells stimulated by endogenous/self, misplaced or altered molecules, belonging to physiological aging. This age-related inflammatory ... ...

Abstract	Inflammaging refers to a chronic, systemic, low-grade inflammation, driven by immune (mainly macrophages) and non-immune cells stimulated by endogenous/self, misplaced or altered molecules, belonging to physiological aging. This age-related inflammatory status is characterized by increased inflammation and decreased macroautophagy/autophagy (a degradation process that removes unnecessary or dysfunctional cell components). Inflammaging predisposes to age-related diseases, including obesity, type-2 diabetes, cancer, cardiovascular and neurodegenerative disorders, as well as vulnerability to infectious diseases and vaccine failure, representing thus a major target for anti-aging strategies. Phenolic compounds-found in extra-virgin olive oil (EVOO)-are well known for their beneficial effect on longevity. Among them, hydroxytyrosol (HTyr) appears to greatly contribute to healthy aging by its documented potent antioxidant activity. In addition, HTyr can modulate inflammation and autophagy, thus possibly counteracting and reducing inflammaging. In this review, we reference the literature on pure HTyr as a modulatory agent of inflammation and autophagy, in order to highlight its possible interference with inflammaging. This HTyr-mediated activity might contribute to healthy aging and delay the development or progression of diseases related to aging.
MeSH term(s)	Humans ; Inflammation ; Olive Oil/pharmacology ; Aging ; Autophagy
Chemical Substances	3,4-dihydroxyphenylethanol (10597-60-1) ; Olive Oil
Language	English
Publishing date	2023-04-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15071774
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Natural Polyphenols as Immunomodulators to Rescue Immune Response Homeostasis: Quercetin as a Research Model against Severe COVID-19.

Bernini, Roberta / Velotti, Francesca

Molecules (Basel, Switzerland)

2021 Volume 26, Issue 19

Abstract: The COVID-19 pandemic is caused by SARS-CoV-2 and is leading to the worst health crisis of this century. It emerged in China during late 2019 and rapidly spread all over the world, producing a broad spectrum of clinical disease severity, ranging from ... ...

Abstract	The COVID-19 pandemic is caused by SARS-CoV-2 and is leading to the worst health crisis of this century. It emerged in China during late 2019 and rapidly spread all over the world, producing a broad spectrum of clinical disease severity, ranging from asymptomatic infection to death (4.3 million victims so far). Consequently, the scientific research is devoted to investigating the mechanisms of COVID-19 pathogenesis to both identify specific therapeutic drugs and develop vaccines. Although immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, new understanding has emerged about the innate and adaptive immune responses elicited in SARS-CoV-2 infection, which are mainly focused on the dysregulated inflammatory response in severe COVID-19. Polyphenols are naturally occurring products with immunomodulatory activity, playing a relevant role in reducing inflammation and preventing the onset of serious chronic diseases. Mainly based on data collected before the appearance of SARS-CoV-2, polyphenols have been recently suggested as promising agents to fight COVID-19, and some clinical trials have already been approved with polyphenols to treat COVID-19. The aim of this review is to analyze and discuss the in vitro and in vivo research on the immunomodulatory activity of quercetin as a research model of polyphenols, focusing on research that addresses issues related to the dysregulated immune response in severe COVID-19. From this analysis, it emerges that although encouraging data are present, they are still insufficient to recommend polyphenols as potential immunomodulatory agents against COVID-19.
MeSH term(s)	Adaptive Immunity/drug effects ; Animals ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; COVID-19/immunology ; Humans ; Immunity, Innate/drug effects ; Immunologic Factors/chemistry ; Immunologic Factors/pharmacology ; Immunologic Factors/therapeutic use ; Polyphenols/chemistry ; Polyphenols/pharmacology ; Polyphenols/therapeutic use ; Quercetin/analogs & derivatives ; Quercetin/pharmacology ; Quercetin/therapeutic use ; SARS-CoV-2/drug effects ; SARS-CoV-2/immunology
Chemical Substances	Antiviral Agents ; Immunologic Factors ; Polyphenols ; Quercetin (9IKM0I5T1E)
Language	English
Publishing date	2021-09-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules26195803
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Article ; Online: Editorial: Cellular Stress and Inflammation: How the Immune System Drives Tissue Homeostasis.

Antonangeli, Fabrizio / Grimsholm, Ola / Rossi, Marianna Nicoletta / Velotti, Francesca

Frontiers in immunology

2021 Volume 12, Page(s) 668876

MeSH term(s)	Animals ; Cell Communication ; Epithelial-Mesenchymal Transition ; Extracellular Matrix/immunology ; Extracellular Matrix/metabolism ; Extracellular Matrix/pathology ; Homeostasis ; Humans ; Immune System/immunology ; Immune System/metabolism ; Immune System/pathology ; Inflammation/immunology ; Inflammation/metabolism ; Inflammation/pathology ; Inflammation Mediators/metabolism ; Signal Transduction ; Stress, Physiological/immunology
Chemical Substances	Inflammation Mediators
Language	English
Publishing date	2021-03-18
Publishing country	Switzerland
Document type	Editorial ; Introductory Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.668876
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Article ; Online: Perspectives on Populus spp. (Salicaceae) bud extracts as antioxidant and anti-inflammatory agents

Pannucci, Elisa / D’Eliseo, Donatella / Ieri, Francesca / Romani, Annalisa / Santi, Luca / Bernini, Roberta / Sabatti, Maurizio / Velotti, Francesca

Natural Product Research. 2022 Mar. 19, v. 36, no. 6 p.1648-1652

2022

Abstract: Hydroalcoholic extracts obtained from buds of P. nigra, P. deltoides and P. trichocarpa were characterized by HPLC-DAD-MS analysis and subsequently evaluated in vitro for their antioxidant and anti-inflammatory activities. ABTS and DPPH assays evidenced ... ...

Abstract	Hydroalcoholic extracts obtained from buds of P. nigra, P. deltoides and P. trichocarpa were characterized by HPLC-DAD-MS analysis and subsequently evaluated in vitro for their antioxidant and anti-inflammatory activities. ABTS and DPPH assays evidenced that P. nigra showed the best antioxidant activity in line with its highest total phenolic content. The analysis of the anti-inflammatory activity clearly demonstrated that all extracts suppressed the production of key pro-inflammatory cytokines (IL-6, Il-1β and TNF-α) and HMGB1 inflammatory danger signal. These results show antioxidant and critical anti-inflammatory activities mediated by the extracts, emphasising their potentiality as therapeutic agents.
Keywords	Populus ; anti-inflammatory activity ; antioxidant activity ; antioxidants ; interleukin-6 ; nucleoproteins ; research ; therapeutics ; Poplar ; buds’ extracts ; phenolic compounds
Language	English
Dates of publication	2022-0319
Size	p. 1648-1652.
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	2185747-7
ISSN	1478-6427 ; 1478-6419
ISSN (online)	1478-6427
ISSN	1478-6419
DOI	10.1080/14786419.2021.1896512
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Article ; Online: Granzyme B in Inflammatory Diseases: Apoptosis, Inflammation, Extracellular Matrix Remodeling, Epithelial-to-Mesenchymal Transition and Fibrosis.

Velotti, Francesca / Barchetta, Ilaria / Cimini, Flavia Agata / Cavallo, Maria Gisella

Frontiers in immunology

2020 Volume 11, Page(s) 587581

Abstract: Inflammation is strictly interconnected to anti-inflammatory mechanisms to maintain tissue homeostasis. The disruption of immune homeostasis can lead to acute and chronic inflammatory diseases, as cardiovascular, pulmonary, metabolic diseases and cancer. ...

Abstract	Inflammation is strictly interconnected to anti-inflammatory mechanisms to maintain tissue homeostasis. The disruption of immune homeostasis can lead to acute and chronic inflammatory diseases, as cardiovascular, pulmonary, metabolic diseases and cancer. The knowledge of the mechanisms involved in the development and progression of these pathological conditions is important to find effective therapies. Granzyme B (GrB) is a serine protease produced by a variety of immune, non-immune and tumor cells. Apoptotic intracellular and multiple extracellular functions of GrB have been recently identified. Its capability of cleaving extracellular matrix (ECM) components, cytokines, cell receptors and clotting proteins, revealed GrB as a potential multifunctional pro-inflammatory molecule with the capability of contributing to the pathogenesis of different inflammatory conditions, including inflammaging, acute and chronic inflammatory diseases and cancer. Here we give an overview of recent data concerning GrB activity on multiple targets, potentially allowing this enzyme to regulate a wide range of crucial biological processes that play a role in the development, progression and/or severity of inflammatory diseases. We focus our attention on the promotion by GrB of perforin-dependent and perforin-independent (anoikis) apoptosis, inflammation derived by the activation of some cytokines belonging to the IL-1 cytokine family, ECM remodeling, epithelial-to-mesenchymal transition (EMT) and fibrosis. A greater comprehension of the pathophysiological consequences of GrB-mediated multiple activities may favor the design of new therapies aim to inhibit different inflammatory pathological conditions such as inflammaging and age-related diseases, EMT and organ fibrosis.
MeSH term(s)	Animals ; Apoptosis ; Epithelial-Mesenchymal Transition ; Extracellular Matrix ; Fibrosis ; Granzymes/immunology ; Humans ; Inflammation/immunology ; Perforin/immunology
Chemical Substances	Perforin (126465-35-8) ; GZMB protein, human (EC 3.4.21.-) ; Granzymes (EC 3.4.21.-)
Language	English
Publishing date	2020-11-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.587581
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Article: Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy.

D'Eliseo, Donatella / Velotti, Francesca

Journal of clinical medicine

2016 Volume 5, Issue 2

Abstract: Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional cytotoxic therapies lead to unsatisfactory long-term survival, mainly related to development of drug resistance by tumor cells and toxicity towards normal cells. n-3 ... ...

Abstract	Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional cytotoxic therapies lead to unsatisfactory long-term survival, mainly related to development of drug resistance by tumor cells and toxicity towards normal cells. n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can exert anti-neoplastic activity by inducing apoptotic cell death in human cancer cells either alone or in combination with conventional therapies. Indeed, n-3 PUFAs potentially increase the sensitivity of tumor cells to conventional therapies, possibly improving their efficacy especially against cancers resistant to treatment. Moreover, in contrast to traditional therapies, n-3 PUFAs appear to cause selective cytotoxicity towards cancer cells with little or no toxicity on normal cells. This review focuses on studies investigating the cytotoxic activity of n-3 PUFAs against cancer cells via apoptosis, analyzing the molecular mechanisms underlying this effective and selective activity. Here, we highlight the multiple molecules potentially targeted by n-3 PUFAs to trigger cancer cell apoptosis. This analysis can allow a better comprehension of the potential cytotoxic therapeutic role of n-3 PUFAs against cancer, providing specific information and support to design future pre-clinical and clinical studies for a better use of n-3 PUFAs in cancer therapy, mainly combinational therapy.
Language	English
Publishing date	2016-01-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm5020015
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Article ; Online: Perspectives on

Pannucci, Elisa / D'Eliseo, Donatella / Ieri, Francesca / Romani, Annalisa / Santi, Luca / Bernini, Roberta / Sabatti, Maurizio / Velotti, Francesca

Natural product research

2021 Volume 36, Issue 6, Page(s) 1648–1652

Abstract: Hydroalcoholic extracts obtained from buds ... ...

Abstract	Hydroalcoholic extracts obtained from buds of
MeSH term(s)	Anti-Inflammatory Agents/pharmacology ; Antioxidants/chemistry ; Antioxidants/pharmacology ; Plant Extracts/chemistry ; Plant Extracts/pharmacology ; Populus/chemistry ; Salicaceae
Chemical Substances	Anti-Inflammatory Agents ; Antioxidants ; Plant Extracts
Language	English
Publishing date	2021-03-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2185747-7
ISSN	1478-6427 ; 1478-6419
ISSN (online)	1478-6427
ISSN	1478-6419
DOI	10.1080/14786419.2021.1896512
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Article: In vitro studies on anti-inflammatory activities of kiwifruit peel extract in human THP-1 monocytes

D’Eliseo, Donatella / Bernini, Roberta / Campo, Margherita / Pannucci, Elisa / Romani, Annalisa / Santi, Luca / Velotti, Francesca

Journal of ethnopharmacology. 2019 Apr. 06, v. 233

2019

Abstract: Kiwifruit is native to eastern China and many are the references about the consumption of fruits and fruits extracts of the Actinidia plants in Chinese traditional medicine as therapeutic food supplements to prevent and/or counteract numerous disorders ... ...

Abstract	Kiwifruit is native to eastern China and many are the references about the consumption of fruits and fruits extracts of the Actinidia plants in Chinese traditional medicine as therapeutic food supplements to prevent and/or counteract numerous disorders including inflammation-related diseases like cancer.Aim of the present work was to obtain a kiwifruit peel extract, rich in polyphenols, and to explore the anti-inflammatory potential by analyzing its capability to target multiple pathways involved in monocyte-mediated inflammatory response.The extract was obtained from the fruit peel of Actinidia deliciosa (A.Chev.) C.F.Liang & A.R.Ferguson, cv Hayward and characterized by HPLC-DAD-ESI-MS. Lipopolysaccharide-stimulated THP-1 monocytes were used as a model of human inflammation in vitro.Analytical data evidenced that procyanidins resulted the main polyphenols present in the extract, representing the 92% w/w of the total. The extract inhibited the production of inflammatory molecules such as IL-6, IL-1β, TNF-α pro-inflammatory cytokines, HMGB1 danger signal and granzyme B serine protease by activated monocytes. In particular, an inhibitory activity of 81%, 68%, 63%, 76% and 60% on the extracellular release of IL-6, IL-1β, TNF-α, HMGB1 and granzyme B, respectively, was observed by western blot analysis. Moreover, the extract prevented STAT3 activation and promoted autophagy.The reported findings demonstrated a strong and broad anti-inflammatory profile of the kiwifruit peel extract, which makes it a promising preventive and therapeutic natural ingredient for nutraceutical, cosmetic and pharmaceutical formulations to counteract multiple inflammatory disorders.
Keywords	Actinidia deliciosa ; anti-inflammatory activity ; dietary supplements ; dietetic foods ; drug formulations ; fruit extracts ; fruit peels ; fruits ; functional foods ; in vitro studies ; inflammation ; ingredients ; interleukin-1beta ; interleukin-6 ; kiwifruit ; models ; monocytes ; nucleoproteins ; procyanidins ; serine proteinases ; therapeutics ; traditional medicine ; tumor necrosis factor-alpha ; Western blotting ; China
Language	English
Dates of publication	2019-0406
Size	p. 41-46.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2018.12.044
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Increased circulating granzyme B in type 2 diabetes patients with low-grade systemic inflammation.

Cimini, Flavia Agata / D'Eliseo, Donatella / Barchetta, Ilaria / Bertoccini, Laura / Velotti, Francesca / Cavallo, Maria Gisella

Cytokine

2018 Volume 115, Page(s) 104–108

Abstract: In metabolic diseases, like type 2 diabetes (T2D), adipose tissue (AT) is infiltrated by macrophages and other leukocytes - which secrete many bioactive peptides leading to local and systemic low-grade chronic inflammation - and undergoes remodeling and ... ...

Abstract	In metabolic diseases, like type 2 diabetes (T2D), adipose tissue (AT) is infiltrated by macrophages and other leukocytes - which secrete many bioactive peptides leading to local and systemic low-grade chronic inflammation - and undergoes remodeling and aberrant fibrosis. Granzyme B (GrB) is a serine protease produced by some leukocytes, including cytotoxic lymphocytes and macrophages. It exerts both intracellular apoptotic function and extracellular functions, leading to tissue injury, inflammation and repair. Elevated circulating GrB levels have been found in aging- and inflammation-associated diseases and a role for GrB in the pathogenesis of several chronic inflammatory diseases has been reported. Aims of this study were to investigate circulating GrB levels in T2D patients in relation to their systemic inflammatory profile and to unravel its correlates. For this cross-sectional study, we recruited 51 consecutive T2D patients referring to our diabetes outpatient clinics (Sapienza University, Rome, Italy) for metabolic evaluations, and 29 sex, age and body mass index comparable non-diabetic subjects as control group. Study participants underwent clinical work-up; fasting blood sampling was performed for routine biochemistry and for inflammatory profile (CRP, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, GM-CSF, adiponectin, WISP1); serum GrB was measured by Human Granzyme-B Platinum Elisa kit (Affymetrix EBIO). We found that T2D patients had serum levels of GrB significantly higher than the control group (10.17 ± 12.6 vs 7.2 ± 14.1 pg/ml, p = 0.03). Moreover, in T2D patients increased GrB correlated with unfavorable inflammatory profile, as described by elevated levels of validated adipokines such as IL-6 (p = 0.04), TNF-α (p = 0.019) and WISP1 (p = 0.005). Furthermore, multivariate linear regression analysis showed that increased GrB was associated with T2D diagnosis independently from possible confounders. In conclusion, our results show that increased levels of circulating GrB are associated with T2D diagnosis and correlates with markers of AT-linked systemic inflammation, suggesting a potential role for GrB in the inflammatory and reactive processes occurring in metabolic diseases.
MeSH term(s)	Adipokines/blood ; Adiponectin/blood ; Adipose Tissue/metabolism ; Biomarkers/blood ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/metabolism ; Female ; Granzymes/blood ; Humans ; Inflammation/blood ; Inflammation/metabolism ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha/blood
Chemical Substances	Adipokines ; Adiponectin ; Biomarkers ; Tumor Necrosis Factor-alpha ; Granzymes (EC 3.4.21.-)
Language	English
Publishing date	2018-11-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1018055-2
ISSN	1096-0023 ; 1043-4666
ISSN (online)	1096-0023
ISSN	1043-4666
DOI	10.1016/j.cyto.2018.11.019
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Article: Docosahexaenoic acid (DHA) promotes immunogenic apoptosis in human multiple myeloma cells, induces autophagy and inhibits STAT3 in both tumor and dendritic cells.

D'Eliseo, Donatella / Di Renzo, Livia / Santoni, Angela / Velotti, Francesca

Genes & cancer

2016 Volume 8, Issue 1-2, Page(s) 426–437

Abstract: Docosahexaenoic acid (DHA), a ω-3 polyunsaturated fatty acid found in fish oil, is a multi-target agent and exerts anti-inflammatory and anticancer activities alone or in combination with chemotherapies. Combinatorial anticancer therapies, which induce ... ...

Abstract	Docosahexaenoic acid (DHA), a ω-3 polyunsaturated fatty acid found in fish oil, is a multi-target agent and exerts anti-inflammatory and anticancer activities alone or in combination with chemotherapies. Combinatorial anticancer therapies, which induce immunogenic apoptosis, autophagy and STAT3 inhibition have been proposed for long-term therapeutic success. Here, we found that DHA promoted immunogenic apoptosis in multiple myeloma (MM) cells, with no toxicity on PBMCs and DCs. Immunogenic apoptosis was shown by the emission of specific DAMPs (CRT, HSP90, HMGB1) by apoptotic MM cells and the activation of their pro-apoptotic autophagy. Moreover, immunogenic apoptosis was directly shown by the activation of DCs by DHA-induced apoptotic MM cells. Furthermore, we provided the first evidence that DHA activated autophagy in PBMCs and DCs, thus potentially acting as immune stimulator and enhancing processing and presentation of tumor antigens by DCs. Finally, we found that DHA inhibited STAT3 in MM cells. STAT3 pathway, essential for MM survival, contributed to cancer cell apoptosis by DHA. We also found that DHA inhibited STAT3 in blood immune cells and counteracted STAT3 activation by tumor cell-released factors in PBMCs and DCs, suggesting the potential enhancement of the anti-tumor function of multiple immune cells and, in particular, that of DCs.
Language	English
Publishing date	2016-12-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2538519-7
ISSN	1947-6027 ; 1947-6019
ISSN (online)	1947-6027
ISSN	1947-6019
DOI	10.18632/genesandcancer.131
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